Lipidomic analysis as a tool for a comprehensive description of atherosclerotic plaques

Atherosclerosis is a chronic inflammatory disease characterised by the accumulation of lipids and the formation of fibrous plaques in the walls of the medium and large arteries. Consequently, lipids play a crucial role in the development of coronary heart disease and ischemic stroke, two leading causes of mortality in Western societies. This study aimed to develop a strategy for comprehensive characterisation of the lipidome of carotid atherosclerotic plaques in anatomically defined sections and to identify lipid species associated with severity of stenosis, plaque symptomatic status, and sex-related differences. Transverse sections obtained from 22 human atherosclerotic plaques were analysed using ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry. The selection of lipid markers was performed using a combination of univariate statistical approaches and multivariate methods. A total of 431 lipid species were identified in 26 lipid classes in atherosclerotic plaques. Ether and ester-linked glycerophospholipids containing polyunsaturated fatty acids showed negative associations with the severity of stenosis. Regions of maximal stenosis were characterised by lower levels of cholesteryl esters, ether- and ester-linked diacylglycerophosphoethanolamines and diacylglycerophosphoglycerols, glycerophosphoinositols and monoacylglycerophoshocholines were higher in symptomatic plaques. Sex had only a limited effect on the plaque lipidome, and no significant sex-related differences in the association of lipids with stenosis were detected. Together, these findings provide insights into the lipid composition in atherosclerotic plaques and demonstrate the applicability of a section-based analytical approach for detailed plaque characterisation. Lipid species associated with the severity of stenosis and with symptomatic status were identified, whereas sex-related differences in the plaque lipidome were limited. Clinical trial not applicable.